Synthesis of Benzylidene Analogs of Oleanolic Acid as Potential α-Glucosidase and α-Amylase Inhibitors

Lin, Jing; Zhang, Xin; Wu, Xiao-Zheng; Zheng, Yingying; Hu, Chunmei; Kang, Yu; Zhang, Kun; Xiong, Zhuang; Ma, Zhiqiang

doi:10.3389/fchem.2022.911232

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…Among the various classes of compounds obtained from natural resources, triterpenoids also show potent antidiabetic activity, including α-glucosidaseinhibiting effects [8][9][10][11]. For example, oleanolic acid (OA) derivatives, such as oxime esters, showed inhibitory activities against α-glucosidase and α-amylase [12], a series of benzylidene derivatives exhibited excellent to moderate inhibitory effects, and inhibition kinetics results showed that the leading analogs were reversible and mixed-type inhibitors of α-glucosidase and α-amylase [13,14]. OA indole derivatives with various electronwithdrawing groups possessed anti-α-glucosidase activities and demonstrated the capacity to form ligand-enzyme complexes with α-glucosidase enzymes [15].…”

Section: Introductionmentioning

confidence: 99%

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

et al. 2023

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Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

et al. 2023

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“…In addition, OA had been reported to have α‐glucosidase inhibitory activity [23] . Recently, OA was also taken as a parent compound to be modified structurally as its benzylidene, oxime ester, or indole derivatives, which resulted in the generation of other more potent α‐glucosidase inhibitors [24–26] . Besides, the pyrazole group is also discovered to be one key pharmacophore frequently fused a variety of bioactive compounds represented by the marketed drug sildenafil, [27] and some pyrazole‐fused qunazolinone, benzofuran, pyran were reported to exhibit inhibitory activity against α‐glucosidase [28–30] …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Substituted Pyrazole‐Fused Oleanolic Acid Derivatives as Novel Selective α‐Glucosidase Inhibitors

Gao

Liu

et al. 2023

Chemistry & Biodiversity

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A series of novel substituted pyrazole-fused oleanolic acid derivative were synthesized and evaluated as selective α-glucosidase inhibitors. Among these analogs, compounds 4a-4f exhibited more potent inhibitory activities compared with their methyl ester derivatives, and standard drugs acarbose and miglitol as well. Besides, all these analogs exhibited good selectivity towards α-glucosidase over α-amylase. Analog 4d showed potent inhibitory activity against α-glucosidase (IC 50 = 2.64 � 0.13 μM), and greater selectivity towards αglucosidase than α-amylase by ~33-fold. Inhibition kinetics showed that compound 4d was a non-competitive α-glucosidase inhibitor, which was consistent with the result of its simulation molecular docking. Moreover, the in vitro cytotoxicity of compounds 4a-4f towards hepatic LO2 and HepG2 cells was tested.

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Antidiabetic and antioxidant studies of novel synthesized titanium (IV) complex: Design, synthesis, in‐silico docking and in‐vitro studies

Kaushal,

Kaur,

Kumar

et al. 2024

Applied Organom Chemis

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[{TiCl3}2(C3N3S3H)] (where C3N3S3H is Trithiocyanuric acid) was designed and synthesized by the reaction of TiCl4 and trithiocyanuric acid in 2:1 M ratio under stirring and refluxing condition using THF solvent. The synthesized Titanium (IV) complex was characterized by various spectroscopic techniques like FT‐IR, NMR, MASS, XRD, UV–visible spectrophotometer and elemental analysis (CHNSO). Moreover, in‐silico docking studies of the ligand and its Ti (IV) complex were carried out by AutoDockTools‐1.5.6 to study interactions of the complex under study with the receptor protein. Afterwards, both ligand and synthesized Ti (IV)complex were screened for the antioxidant and antidiabetic potential by in‐vitro method. The antioxidant potential was investigated by using DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging assay where ligand exhibited moderate activity while Ti (IV) complex presented significant antioxidant activity. Following, alpha‐amylase enzyme inhibition was investigated using iodine‐starch inhibition assay. It was found that the ligand was inactive (showed no α‐amylase inhibition activity) while the Ti (IV)complex was a potent α‐amylase inhibitor. Furthermore, the experimentally obtained results were also complimented by the in‐silico results.

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Synthesis of Benzylidene Analogs of Oleanolic Acid as Potential α-Glucosidase and α-Amylase Inhibitors

Cited by 4 publications

References 43 publications

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

Synthesis and Biological Evaluation of Substituted Pyrazole‐Fused Oleanolic Acid Derivatives as Novel Selective α‐Glucosidase Inhibitors

Antidiabetic and antioxidant studies of novel synthesized titanium (IV) complex: Design, synthesis, in‐silico docking and in‐vitro studies

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